Interferon α/β modulation of growth‐factor‐stimulated mitogenicity in AKR‐2B fibroblasts

Growth factor‐stimulated mitogenicity in mouse embryo‐derived AKR‐2B cells was inhibited in a dose‐dependent fashion by a mixture of alpha and beta mouse interferons (IFN). A 60% decrease in epidermal growth factor (EGF) and insulin‐stimulated DNA synthesis was observed with 10 kU/ml IFN, and half‐maximal inhibition was seen at 1 kU/ml. Likewise, the mitogenic effect of 5% fetal bovine serum (FBS) was inhibited by 60% with 10 kU/ml IFN and by 38% with 1 kU/ml IFN. IFN inhibition of DNA synthesis was paralleled by a decrease in monolayer growth of AKR‐2B cells by 60% on the 3rd day of culture and by 40% on the 6th day of culture. Soft agar growth of two AKR‐2B derived lines, AKR‐MCA and AKR‐2B (clone 84A), was also inhibited significantly with the addition of 1–10 kU/ml of IFN. The effect of IFN on EGF receptors was also examined. Treatment of AKR‐2B cells with 10 kU/ml IFN resulted in a 35% decrease in EGF binding to cell surface receptors. The reduced binding of EGF to cells treated with IFN was due to a loss of EGF receptors as determined by Scatchard analysis. IFN treatment of AKR‐2B cells neither altered the affinity of the EGF receptor for its ligand nor affected receptor internalization. Nuclear transcription and actinomycin D decay analysis indicated that within 2 hr, IFN reduced c‐myc messenger RNA levels at the level of transcription with no affect on message decay.